A Case of Pancreatic Ductal Adenocarcinoma in an Elderly Adult With Heterotaxy Syndrome

Heterotaxy is a syndrome characterized by a spectrum of anatomical anomalies in organ lateralization due to embryological errors. It frequently involves intrathoracic organs, especially the heart, leading to congenital abnormalities. Abdominal organs can also be affected, causing clinical features such as sepsis from asplenia or intestinal volvulus; however, these are less studied. Currently, there is no data on the relationship between heterotaxy and malignancy. We present an interesting case of an elderly adult admitted for a workup of newly diagnosed pancreatic ductal carcinoma, who was found to have heterotaxy of the stomach and spleen, with eventual tumor invasion of these organs. This case suggests that heterotaxy may increase the risk of gastrointestinal malignancy and result in a poorer prognosis due to the complexity of tumor resection involving additional organs.


Introduction
Heterotaxy is a rare finding and defined as an anatomical variant of intrathoracic and abdominal organs from the typical arrangement that is caused by disruption of left-right axis orientation during embryonic development [1,2].It is most commonly associated with congenital cardiac malformation, but could involve abdominal organs such as the spleen, stomach, and liver [3].Current data regarding non-cardiac heterotaxy are very limited including association with GI malignancy, although case reports do mention a few cases of atrophied pancreas in patients with heterotaxy.We present a case of an elderly adult with pancreatic ductal adenocarcinoma who was found to have heterotaxy of the stomach and spleen.

Case Presentation
A 69-year-old female with past medical history of type-2 diabetes mellitus and recent finding of mass in the pancreatic head from outpatient CT scan of the abdomen and pelvis (CTAP) a month ago without further workup, presented with progressively worsening generalized abdominal pain of 4 months duration She was subsequently admitted for symptom management and malignancy workup.Physical examination revealed generalized abdominal tenderness most prominently in the epigastric region, but no alarming features.Initial vital signs and routine blood work were unremarkable.CTAP with intravenous contrast showed a 5.3 x 6.3 x 6.7 cm hypodense pancreatic mass centered in the pancreatic head and uncinate process abutting right margin of superior mesenteric artery, right kidney right adrenal mass, portions of duodenum and jejunum and less curvature of stomach.Interestingly, the stomach was found to be in the right upper quadrant (RUQ) with loss of a discernable fat plane with associated mural thickening, as well as polysplenic appearance in the RUQ, which the patient was not aware of previously.Upon obtaining baseline past records, a CT AP from 2 years ago already showed stomach and spleen tissues in the RUQ and severe pancreatic atrophy.While inpatient, EUS with biopsy demonstrated 6 mm pancreatic ductal 6 mm dilatation and confirmed the diagnosis of pancreatic ductal adenocarcinoma, as well as visualization of pancreatic body and tail atrophy.She was discharged and completed two cycles of FOLFIRINOX chemotherapy regimen in the anticipation of downsizing the tumor for possible future resection.However, the patient's functional status was worsening and had numerous hospital visits for intractable abdominal pain and small bowel obstruction.She was eventually enrolled into a hospice program.Four months after the first visit, the patient was admitted again for poorly controlled abdominal cancer pain and transitioned to inpatient hospice.On the last admission, a repeated CTAP revealed a pancreas mass that was 9.0 x 8.1 cm x 7.6 cm in size with central necrosis, complete circumferential encasement of the proximal duodenum with fistulization, representing further worsening of previously known organ invasions, as well as new invasion to the spleen on RUQ.

Discussion
Most studies of heterotaxy syndrome are related to congenital cardiac abnormalities such as isomerism of atrial appendages in neonatal populations with a high morbidity and mortality rate [4].For abdominal organs, spleen (asplenia or polysplenia), liver, stomach, and intestinal tract were reported to be in abnormal positions with potential clinical features such as sepsis from asplenia or intestinal volvulus [5].In this case, the patient had incidental and asymptomatic findings of stomach and spleen, likely the reason she remained relatively healthy until this age.Mentions of an association between pancreas and heterotaxy were only sporadic in the literature and none with pancreatic malignancy.There are case reports of patients of heterotaxy with polysplenia concomitantly showing agenesis of the dorsal pancreas but without pancreatic malignancy [6].Although in the general population pancreatic atrophy is known to be associated with pancreatic cancer, in most cases the tumor arises from the same location as the atrophy [7].In our case, the tumor is in the pancreatic head and uncinate process while the baseline atrophy was in the body and tail.We hypothesize that patients with abdominal heterotaxy have increased risk of pancreatic malignancy compared to the general population indicating a need for more research regarding this.Furthermore, extra organs make tumor resection more difficult hence a poorer prognosis, as in this case the pancreatic tumor was invading the stomach and spleen in the RUQ.Lastly, the patient had the findings of heterotaxy and atrophic pancreas with known diabetes years prior developing malignancy but no screening, as there is no current guideline regarding screening in this condition.

Conclusions
In conclusion, due to the uncommon occurrence of heterotaxy syndrome, there is limited data available, particularly concerning abdominal organs.This case suggests a possible association between heterotaxy syndrome and cancer, with potentially worse complications for the patient due to the proximity of extra organs to tumors may impede surgical resection compared to the general population.Therefore, it is crucial for clinicians to be aware of the potential for associated malignancies when encountering heterotaxy syndrome and for the medical community to promote further research on this condition.

FIGURE 1 :
FIGURE 1: (A) Initial contrast-enhanced CT scan of the abdomen and pelvis (CTAP) revealing the stomach and three splenic tissues located in the right upper quadrant (RUQ) (B) Initial CTAP showing pancreatic head mass abutting lesser curvature of the stomach (C) CTAP four months later with previous pancreatic head mass increased in size with new invasion of spleen in the RUQ